The M-current (I M ), comprised of Kv7 channels, is a voltage-activated K ϩ conductance that plays a key role in the control of cell excitability. In hippocampal principal cells, I M controls action potential (AP) accommodation and contributes to the medium-duration afterhyperpolarization, but the role of I M in control of interneuron excitability remains unclear. Here, we investigated I M in hippocampal stratum oriens (SO) interneurons, both from wild-type and transgenic mice in which green fluorescent protein (GFP) was expressed in somatostatin-containing interneurons. Somatodendritic expression of Kv7.2 or Kv7.3 subunits was colocalized in a subset of GFPϩ SO interneurons, corresponding to oriens-lacunosum moleculare (O-LM) cells. Under voltage clamp (VC) conditions at Ϫ30 mV, the Kv7 channel antagonists linopirdine/XE-991 abolished the I M amplitude present during relaxation from Ϫ30 to Ϫ50 mV and reduced the holding current (I hold ). In addition, 0.5 mM tetraethylammonium reduced I M , suggesting that I M was composed of Kv7.2-containing channels. In contrast, the Kv7 channel opener retigabine increased I M amplitude and I hold . When strongly depolarized in VC, the linopirdine-sensitive outward current activated rapidly and comprised up to 20% of the total current. In current-clamp recordings from GFPϩ SO cells, linopirdine induced depolarization and increased AP frequency, whereas retigabine induced hyperpolarization and arrested firing. In multicompartment O-LM interneuron models that incorporated I M , somatodendritic placement of Kv7 channels best reproduced experimentally measured I M . The models suggest that Kv3-and Kv7-mediated channels both rapidly activate during single APs; however, Kv3 channels control rapid repolarization of the AP, whereas Kv7 channels primarily control the interspike interval.

It is well known that interneurons are heterogeneous in their morphologies, biophysical properties, pharmacological sensitivities and electrophysiological responses, but it is unknown how best to understand this diversity. Given their critical roles in shaping brain output, it is important to try to understand the functionality of their computational characteristics. To do this, we focus on specific interneuron subtypes. In particular, it has recently been shown that long‐term potentiation is induced specifically on oriens‐lacunosum/moleculare (O‐LM) interneurons in hippocampus CA1 and that the same cells contain the highest density of dendritic sodium and potassium conductances measured to date. We have created multi‐compartment models of an O‐LM hippocampal interneuron using passive properties, channel kinetics, densities and distributions specific to this cell type, and explored its signalling characteristics. We found that spike initiation depends on both location and amount of input, as well as the intrinsic properties of the interneuron. Distal synaptic input always produces strong back‐propagating spikes whereas proximal input could produce both forward‐ and back‐propagating spikes depending on the input strength. We speculate that the highly active dendrites of these interneurons endow them with a specialized function within the hippocampal circuitry by allowing them to regulate direct and indirect signalling pathways within the hippocampus.

Saraga, Fernanda, Leo Ng, and Frances K. Skinner. Distal gap junctions and active dendrites can tune network dynamics. J Neurophysiol 95: 1669 -1682, 2006. First published December 7, 2005 doi:10.1152/jn.00662.2005. Gap junctions allow direct electrical communication between CNS neurons. From theoretical and modeling studies, it is well known that although gap junctions can act to synchronize network output, they can also give rise to many other dynamic patterns including antiphase and other phase-locked states. The particular network pattern that arises depends on cellular, intrinsic properties that affect firing frequencies as well as the strength and location of the gap junctions. Interneurons or GABAergic neurons in hippocampus are diverse in their cellular characteristics and have been shown to have active dendrites. Furthermore, parvalbumin-positive GABAergic neurons, also known as basket cells, can contact one another via gap junctions on their distal dendrites. Using two-cell network models, we explore how distal electrical connections affect network output. We build multi-compartment models of hippocampal basket cells using NEURON and endow them with varying amounts of active dendrites. Two-cell networks of these model cells as well as reduced versions are explored. The relationship between intrinsic frequency and the level of active dendrites allows us to define three regions based on what sort of network dynamics occur with distal gap junction coupling. Weak coupling theory is used to predict the delineation of these regions as well as examination of phase response curves and distal dendritic polarization levels. We find that a nonmonotonic dependence of network dynamic characteristics (phase lags) on gap junction conductance occurs. This suggests that distal electrical coupling and active dendrite levels can control how sensitive network dynamics are to gap junction modulation. With the extended geometry, gap junctions located at more distal locations must have larger conductances for pure synchrony to occur. Furthermore, based on simulations with heterogeneous networks, it may be that one requires active dendrites if phase-locking is to occur in networks formed with distal gap junctions. Interneurons, or inhibitory GABAergic neurons, in hippocampus are diverse in their cellular characteristics and have been shown and suggested to have active dendrites (Maccaferri et al. 2004;Martina et al. 2000;McBain and Fisahn 2001;Traub and Miles 1995). Furthermore, parvalbumin-positive GABAergic neurons, also known as basket cells, are known to contact one another via gap junctions on their distal dendrites Kosaka 2000, 2003;Katsumaru et al. 1988;Kosaka and Hama 1985). Because gap junctions represent a form of direct, bidirectional electrical communication, it is reasonable to think of their primary role as that of mediating synchrony. However, theoretical and modeling studies show that although gap junctions can act to synchronize network output in firing (oscillating) neurons, they can also give rise to many...

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